Published online Jul 14, 2022. doi: 10.3748/wjg.v28.i26.3218
Peer-review started: February 3, 2022
First decision: April 10, 2022
Revised: April 22, 2022
Accepted: June 15, 2022
Article in press: June 15, 2022
Published online: July 14, 2022
Processing time: 159 Days and 23.7 Hours
Non-alcoholic steatohepatitis (NASH) cirrhosis is the second leading indication for liver transplantation (LT). There is a conflicted role of body mass index (BMI) on outcomes of NASH cirrhosis while on waitlist and post liver transplant.
There are few reports on the waitlist and post liver transplant outcomes of lean vs obese NASH patients, and the impact of ascites adjusted BMI have not been fully clarified.
The objective of this study was to compare the longitudinal trajectories of patients with lean vs obese NASH cirrhosis, from listing up to post-transplant, having adjusted their BMI for ascites.
A retrospective analysis of all adult NASH patients listed for LT at the University Health Network, Toronto between November 2012 and May 2019 was performed. We summarized the clinical characteristics of patients with lean and obese NASH. Competing risk analyses and Cox Proportional Hazard models were used to assess the cumulative incidence of transplant and survival outcomes.
Out of 265 patients listed for NASH cirrhosis, 176 were included. The median age was 61 (32–71.4) years; 46% were females. 111 patients underwent LT. Lean NASH patients were elderly at time of listing (median age 61.6 years vs 60.3 years, P = 0.048), worse renal functions at end of listing (median estimated glomerular filtration 48 mL/min/1.73 m2 vs 57 mL/min/1.73 m2, P = 0.017), carried more severe ascites (66.6% vs 45%, P = 0.03) and were more paracentesis dependent (72.2% vs 52.9%, P = 0.016). Obese robust patients had better waitlist survival [hazard ratio (HR): 0.12; 95%CI: 0.05–0.29, P < 0.0001] with higher instantaneous rate of transplant (HR: 5.71; 95%CI: 1.26–25.9, P = 0.02). Lean NASH patients had a substantially higher risk of graft loss within 90 d post-LT (1.2% vs 13.8%, P = 0.032) and death post-LT (2.4% vs 17.2%, P = 0.029). 1- 3- and 5-year graft survival was poor for lean NASH (78.6%, 77.3% and 41.7% vs 98.6%, 96% and 85% respectively). Overall patient survival post-LT was significantly worse in lean NASH (HR: 0.17; 95%CI: 0.03–0.86, P = 0.0142) with 83% lower instantaneous rate of death in obese group. Post-transplant renal function was significantly better in lean NASH patients at 5 years (median creatinine 111 μmol/L vs 153.5 μmol/L, P = 0.019).
Although lean NASH was thought to be more benign than obese NASH, our study suggests a paradoxical correlation of lean NASH with waitlist outcomes, and graft and patient survival post-LT, in conjunction with often comorbid frailty.
To understand the underlying molecular mechanisms linking lean NASH with worse outcomes, there is need of identifying the factors such as genetic variants, body fat distribution/visceral adiposity, which can play role in this paradox.